Acetyl-CoA from Inflammation-Induced Fatty Acids Oxidation Promotes Hepatic Malate-Aspartate Shuttle Activity and Glycolysis.

08:00 EDT 15th May 2018 | BioPortfolio

Summary of "Acetyl-CoA from Inflammation-Induced Fatty Acids Oxidation Promotes Hepatic Malate-Aspartate Shuttle Activity and Glycolysis."

Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins. Both mitochondrial glutamate oxaloacetate transaminase 2 (GOT2) and malate dehydrogenase 2 (MDH2) were acetylated, and the malate-aspartate shuttle (MAS) activity was stimulated to maintain glycolysis. By using 13C-carbon tracing in vitro, acetyl-CoA was found to be mainly supplied by lipid-derived fatty acid oxidation rather than glucose-derived pyruvate oxidative decarboxylation, while glucose was mainly used for lactate production in response to inflammatory stress. The results of the mitochondrial experiment showed that acetyl-CoA directly increases MDH2, and in turn, the GOT2 acetylation level affects MAS activity. Treatment with palmitate in primary hepatocytes from LPS-injected pigs increased the hepatic production of acetyl-CoA, pyruvate and lactate; MAS activity; and hepatic MDH2 and GOT2 hyperacetylation, while the deficiency of long-chain acetyl-CoA dehydrogenase (LCAD) resulted in the stabilization of these parameters. These observations suggest that acetyl-CoA produced by fatty acid oxidation promotes MAS activity and glycolysis via non-enzymatic acetylation during the inflammatory stress response.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Endocrinology and metabolism
ISSN: 1522-1555


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Medical and Biotech [MESH] Definitions

Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent.

An enzyme that catalyzes reversibly the hydrolysis of acetyl-CoA to yield CoA and acetate. The enzyme is involved in the oxidation of fatty acids. EC

Enzyme that catalyzes the final step of fatty acid oxidation in which ACETYL COA is released and the CoA ester of a fatty acid two carbons shorter is formed.

Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)

An acetic acid ester of CARNITINE that facilitates movement of ACETYL COA into the matrices of mammalian MITOCHONDRIA during the oxidation of FATTY ACIDS.

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